Instrumental analysis systems and methods

ABSTRACT

Instrumental analysis systems are provided that can include: an analytical attachment axially aligned with a sample upon a sample stage; structure supporting both the attachment and the sample stage; and at least one band affixed to the analytical attachment and aligned symmetrically about the axis of the attachment. Methods for analyzing samples are provided. The methods can include: providing at least one band supported by a structure; firmly affixing an analytical attachment to the band, and axially aligning the attachment with a sample; and providing a temperature gradient between the band and the sample while maintaining axial alignment of the objective and the sample.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. patent application Ser. No.15/457,953 filed Mar. 13, 2017, entitled “Instrumental Analysis Systemsand Methods”, which claims priority to U.S. provisional patentapplication Ser. No. 62/307,260 which was filed Mar. 11, 2016, entitled“Cryogenic Assemblies and Methods”, the entirety of each of which isincorporated by reference herein.

TECHNICAL FIELD

The present disclosure relates to instrumental analysis systems andmethods and in particular embodiments to cryogenic analysis assembliesand methods. In particular embodiments, the present disclosure relatesto systems, assemblies, and/or methods that include the use ofanalytical attachments to instrumental analysis systems, cryogenicassemblies and/or cryostats

BACKGROUND

Instrumental analysis has been used for decades upon decades, and duringthis time, scientists and laboratory personnel alike continue to demandmore and more accuracy from their systems, instruments, and/or methods.The slightest change in alignment between analytical instrumentattachments and a sample to be analyzed can require countless hours ofadditional research and/or lead to poor data which almost always amountsto poor conclusions.

For example, with cryogenic analysis systems such as cryogenicassemblies, researchers utilize analytical attachments to investigatesamples in their frozen state. Many cryogenic researchers use analyticalattachments such as optical microscopy to study single molecules. Thisis achieved by using a microscope objective to focus and/or collectlight from a sample which is held at cryogenic temperatures. Microscopeobjectives are precisely manufactured chains of lenses which areconventionally designed for room-temperature use.

High light collection efficiency also requires the objective to have avery small working distance between its tip and a sample. Researchershave historically traded off objective performance for longer workingdistances to allow the objective to be mounted outside of the cryostat.

The present disclosure provides cryogenic assemblies and methods,embodiments of which overcome one or more of the shortcomings of theprior art.

SUMMARY OF THE DISCLOSURE

Instrumental analysis systems are provided that can include: ananalytical attachment axially aligned with a sample upon a sample stage;structure supporting both the attachment and the sample stage; and atleast one band affixed to the analytical attachment and symmetricallyabout the axis of the attachment.

Methods for analyzing samples are provided. The methods can include:providing at least one band supported by a structure; firmly affixing ananalytical attachment to the band, and axially aligning the attachmentwith a sample; and providing a temperature gradient between the band andthe sample while maintaining axial alignment of the objective and thesample.

DRAWINGS

Embodiments of the disclosure are described below with reference to thefollowing accompanying drawings.

FIG. 1 is a side perspective view of an exemplary cryostation.

FIG. 2 is a top plan view of the cryostation of FIG. 1 according to anembodiment of the disclosure.

FIG. 3 is a side elevational cutaway view of the cryostation of FIG. 1according to an embodiment of the disclosure.

FIG. 4 is a portion of a cryogenic assembly according to an embodiment.

FIG. 5 is another portion of cryogenic assembly according to anembodiment of the disclosure.

FIG. 6 is yet another portion of a cryogenic assembly according to anembodiment of the disclosure.

DESCRIPTION

This disclosure is submitted in furtherance of the constitutionalpurposes of the U.S. Patent Laws “to promote the progress of science anduseful arts” (Article 1, Section 8).

Embodiments of the present disclosure will be described with referenceto FIGS. 1-6. Referring first to FIG. 1, an exemplary cryostation 8 isdepicted. Cryostation 8 can be generally configured as described in U.S.Pat. No. 8,746,008 to Mauritsen et al. and entitled, “Low VibrationCryocooled System for Low Temperature Microscopy and SpectroscopyApplications”, the entirety of which is incorporated by referenceherein. Operators may also utilize Montana Instruments Cryostation™(Montana Instruments, Bozeman, Mont.) with the assemblies of the presentdisclosure to view samples using objectives.

Cryostation 8 can include a support 3 which supports a closed-cyclecryocooler expander unit 4 which can be operatively aligned with samplehousing 1. Unit 4 can be a Sumitomo Heavy Industries RDK-1 OIDcryocooler.

Referring next to FIGS. 2 and 3, spring dampers 5 may be operativelyaligned between unit 4 and support 3. Unit 4 can be connected to samplehousing 1 and cryogenic sample support 11 by bellows 2. The diameter ofbellows 2 can be in the range from about 0.75 inches to about 3 inchesand is more preferably in the range from about 1 inch to about 1.25inches.

In normal use, both rigid support 3 and sample housing 1 rest on anoptical bench 12 or on another rigid plane. In a more preferredembodiment, optical bench 12 is a Newport air isolated workstation.

The sample is preferably supported by a rigid cryogenic support 11 whichholds the sample in a fixed location relative to the optical bench 12 orrigid plane on which the invention rests. The cryocooler also can beattached to the rigid support 11 by a separate flexible hermetic sealingbellows 13 that is in alignment with flexible vacuum bellows 2. Atemperature sensor 14 and a heater 15 may be located on the cryogenicsupport 11 near the sample to allow for an adaptive feedback loop toreduce temperature fluctuations. In at least one embodiment, thetemperature sensor is a Cernox temperature sensor from LakeshoreCryogenics Inc.

In more detail, system 8 allows a sample to be cryogenically cooled andrigidly mounted to the optics bench 12 and aligned separately (situateda distance away) from the axis of the cryocooler expander unit 4 suchthat top access to the sample housing 1 via top access port 6 may beachieved. This unique configuration in which the sample is located offaxis from and a distance away from the cryocooler expander unit 4reduces sample vibration by isolating the sample. The pair of flexiblevacuum bellows 2 and 13 which connect the cryocooler expander unit 4 tothe sample housing 1 and to the rigid support 3 are preferably alignedalong a common axis and opposed to one another such that when there is adifferential pressure on the inner and outer surfaces of the bellows 2,there is no net force imposed on the cryocooler expander unit 4.

The cold stage of a closed-cycle cryocooler fluctuates in temperaturedue to the cyclical alternating pressure of the cooled Helium gas witheach cycle of gas entering and exiting the expander section of thecryocooler. Additionally, the parasitic and active heat loads on thecryocooler cause the cold stage to rise in temperature between eachcycle. Typically, the way to minimize thermal fluctuations in cryogenicsystems is to use a PID control loop; however, this method results in anunnecessary amount of heat input to the system, which significantlyraises the cold stage temperature.

In accordance with example implementations, system 8 can be configuredto include a temperature sensor 14 and a heater 15 located near (by“near,” it is located on the same temperature platform and within 2inches) the sample on the cryogenic support 11 such that temperature canbe read by an electronic device for data acquisition.

Specifically, the cryocooler can be operated manually until thecryogenic support 11 has reached a stable temperature near the desiredmeasurement temperature as measured by the temperature sensor 14. Atthat time the temperature profile of at least one cycle of thecryocooler is recorded. Based on this initial, uncontrolled temperatureprofile, a profile of heater values which is inversely proportional tothe recorded temperature profile is applied using heater 15synchronously with the cryocooler cycle and adjusted for phase relativeto the cryocooler cycle to optimize the temperature minimization.

A second phase of optimization of the heater profile can be obtained bymeasuring the residual cyclical temperature variation of each value ofthe heater profile with sensor 14. A correction factor to each value ofthe heater profile is applied using heater 15 that is proportional toeach measured residual value.

Optical access to the cryocooled sample inside the sample housing 1 canbe through the top optical access port 6 and/or through the side accessports 7. These ports are part of what can be referred to as a viewingassembly that resides above the sample platform or cryogenic support. Inaccordance with example embodiments of the disclosure, this assembly canbe subject to temperature differences between portions of the assembly.

A laser, optics and/or a microscope or other analytical attachments maybe used with system 8 to interrogate and observe a cooled sample, all ofwhich are supported by an optics bench. Operation of the system caninclude cooling the cryocooler expander unit 4 to cryogenic temperaturesand using the optical apertures 6 and/or 7 for observation of the sampleusing attachments such as microscopes or other imaging devices andinterrogation of the sample using lasers or other electromagnetic energypropagation devices along with detection of signals returned by theinterrogated sample. It is important to keep these attachments alignedwith the sample in order to obtain reliable data. Movement of theattachment in relation to the sample can make sample analysis difficult,if not impossible.

Many variations of the disclosure will occur to those skilled in theart. Some variations include an inverted cryocooler expander unit 4 suchthat it would be located underneath the optics bench 12 and extend upthrough a hole in the optics bench, or extend up over the edge of theoptics bench 12. Other variations call for the cryocooler expander unit4 being supported by structure separate from the optics bench 12 wherethe sample housing 1 is located. Additionally, the environmentsurrounding the sample may be altered or changed by adding a magneticfield, high pressure, RF field, or other types of environmentalalterations. All such variations are intended to be within the scope ofthis disclosure.

The applicant recognizes that the prior art use of longer workingdistances places windows between the objective and the sample, and thesewindows can cause aberrations. The applicant recognizes that microscopeuse for extended periods of time can give rise to thermal driftassociated with fluctuations in room temperature. As the mount used tohold the objective warms or cools, its material expands or contracts,causing the objective to go in and out of focus on a sample. Mechanicalvibrations also create problems for researchers. The applicantrecognizes that flimsy mounts can cause the objective to move, relativeto the sample, beyond its optical resolution.

To address these problems recognized by the applicant and theshortcomings of the state of the art of instrumental analysis systemsand/or methods, the present disclosure provides systems that can includean analytical attachment axially aligned with a sample upon a samplestage. At least one example of this is configuration is shown in FIG. 4.The systems can also include a chamber housing both the attachment andthe sample stage. In accordance with at least one exampleimplementation, FIG. 5 depicts a cylindrical chamber that can house theattachment and sample stage of FIG. 4. In a cryogenic analysis method,the chamber may be under vacuum. The systems can include at least oneband about a portion of the housing, the attachment being affixed to theband as shown in FIG. 5.

Referring to FIG. 4, a portion of a cryogenic assembly 40 according toan embodiment of the disclosure is shown that includes an objective 42and a sample 44 upon a stage 46. Objective 42 is an example analyticalattachment and cryogenic assembly 40 is an example component of aninstrumental analysis system. In accordance with exampleimplementations, FIG. 4 depicts an operable alignment of objective 42with sample 44 within a cryogenic assembly. This operable alignment canbe considered an axial alignment. Objective 42 can be a set of opticsand/or lenses that may or may not be bundled, but are configured toprovide a view of sample 44 operatively aligned therewith. Sample 44 canbe a solid sample and stage 46 can be configured to support sample 44 inoperable viewing alignment with objective 42. Objective 42 can be firmlysupported by at least one of the bands shown in FIG. 5, for example.

Objective 42 can be maintained a temperature that is different than thetemperature of its surroundings. For example, the temperature ofobjective 42 can be different than the temperature of the sample and/orstage. Accordingly, there can be a temperature gradient betweenobjective 42 and the sample and/or sample stage. The temperature ofobjective 42 and/or optics and/or lenses and/or lens surfaces ofobjective 42 can be at least 250 K and/or at least 100 K different thansample 44 and/or stage 46. Sample 44 and/or stage 46 can be less thanabout 200 K and in some embodiments maintained at less than 40K and/or atemperature of about 4 K.

As is depicted in FIG. 4, an axis 48 can exist between sample 44 andattachment 42. As depicted, axis 48 extends vertically between thesecomponents. This can be considered the axial alignment of thesecomponents and while shown here with the components above one another,other arrangements are contemplated. For example, the attachment, suchas optics can be arranged to view in the horizontal plane or from theside of sample 44 rather than above. In this arrangement, the axialalignment of the attachment is still important as movement can impactthe view of the sample.

Referring next to FIG. 5, one example portion of a cryogenic assembly 50is shown that includes a structure supports 54 and 56. One or both ofthese bands can be aligned symmetrically about axis 58 which can be anaxis such as axis 48 upon which attachments and samples are aligned. Thebands may be concentrically aligned in relation to one another as well.While support structure 52 is shown as a single construction, it maywell be multiple constructions. Further, support structure 52 is shownas substantially cylindrical, however, non-cylindrical structures thatmay or may not include non-cylindrical bands are also contemplated.Additionally, assembly 50 may form a vacuum chamber housing or may becontained within a vacuum chamber housing. Accordingly, supports 54 and56 can be within a vacuum chamber housing.

In addition, a sample may be aligned along axis 58 and an attachment maybe aligned to view along an axis that is normal to axis 58. In thisalignment, the attachment may well be coupled to one of the structuresupports 54 or 56. In accordance with example implementations, thestructure the attachment is coupled to may be maintained at a constanttemperature.

In accordance with example implementations, assembly 50 can include astructure 52 extending between support such as band 54 and supportstructure 56, such as another band. Band 54 and/or structure 56 can be aportion of a complete piece that includes structure 52, or band 54and/or structure 56 can be separate pieces that are coupled to structure52. Band 54 can take the form of a ring that encompasses structure 52for example. Structure 56 can also take the form of a ring thatencompasses support structure 52, but structure 56 may also take manyother forms such as partially or fully rectangular, for example. Band54, support structure 52, and structure 56 may be symmetrical incomparison with the axis when the entirety of these components is thesame temperature.

In accordance with example implementations, there can be a temperaturegradient between 54 band and structure 56 which may define regions,portions or zones about the assembly of the system. For example, band 54can be associated with one portion 60 and structure 56 can be associatedwith another portion 62. Structure 56 can be firmly affixed to a samplestage for example and a temperature gradient controlled through theseportions by controlling the temperatures of band 54 and structure 56. Inaccordance with example embodiments, support structure 52 can besufficiently pliable to provide support but allow for expansion and/orcontraction of related portions.

As is depicted in FIG. 5, band 54 resides above structure 56. Thisarrangement is for purposes of example only. Other arrangementsincluding band 54 below structure 56 are contemplated as well. Regions60 and 62 are depicted to demonstrate temperature controlled 60 anduncontrolled 62. In the controlled region 60, a cryo environment can beprovided for example. In the uncontrolled region 62 an ambient regioncan be provided, but the regions may both be controlled with substantialtemperature differences existing between them. In accordance with otherimplementations, there may be temperature differences between regions 60and 62, with one or both of the temperatures of each of the regionsbeing thermally controlled. Implementations are contemplated whereinregion 62 is above ambient temperature and region 60 may be at atemperature lower than the temperature of region 62.

As FIG. 5 depicts, an axis 58 can extend within the portion and band 54and structure 56 can have a relationship to this axis. For region 62,the temperature changes can cause structure 56 to expand and/or contractas depicted by the arrows. This change in structure 56 can deformsupport structure 52 and impact band 54 which can impact the relation ofthe attachment with a sample where the attachment is coupled to band 54.However, it has been discovered that where a band is utilized, thisimpact is minimized. For example, in a configuration without a band, asimple coupling of the attachment to a bar along the housing or to thehousing itself, the change in region 62 changes the relation of theattachment to the sample.

Referring next to FIG. 6, region 60 is depicted as part of a viewingassembly that includes a portion configured to receive optics 42.Utilizing bands 54, optics 42 can be restrained in a workingrelationship with a sample.

Although some embodiments are shown to include certain features, theApplicant specifically contemplates that any feature disclosed hereinmay be used together or in combination with any other feature on anyembodiment of the invention. It is also contemplated that any featuremay be specifically excluded from any embodiment of the invention.

The systems of the present disclosure can be utilized to analyze asample. For example, a cylindrical housing having at least one bandabout the cylindrical housing can be provided. An analytical attachmentcan be firmly affixed to the band, and the attachment can be axiallyaligned with a sample within the cylindrical housing. A temperaturegradient can be provided between portions of the cylindrical housingwhile maintaining axial alignment of the objective and the sample.

The methods can also include providing another band about the housing.The one and the other bands can have different temperatures. Inaccordance with example implementations thermal energy can betransferred between the two bands. With these two portions at differenttemperatures, steady optical performance can be maintained between theobjective and the sample. A constant distance can be maintained betweenthe attachment and the sample and/or peak-to-peak displacements of theattachment can be maintained below the diffraction limit.

In compliance with the statute, embodiments of the invention have beendescribed in language more or less specific as to structural andmethodical features. It is to be understood, however, that the entireinvention is not limited to the specific features and/or embodimentsshown and/or described, since the disclosed embodiments comprise formsof putting the invention into effect.

The invention claimed is:
 1. A cryogenic instrumental analysis systemcomprising: an analytical attachment axially aligned with a sample upona sample stage, wherein the sample stage is configured to support asample during cryogenic analysis; structure supporting both theattachment and the sample stage; one band affixed to the analyticalattachment and aligned symmetrically about the axis of the attachment;and another band structurally supported about the sample stage, theinstrument configured to maintain the one and the other bands atdifferent temperatures and flowing thermal energy between the two bands.2. The system of claim 1 wherein the other band is structurallysupported and symmetrically aligned about the sample stage, the one andthe other bands defining portions of the system, and the one and theother portions having different temperatures.
 3. The system of claim 2wherein the temperature of the one band is greater than the temperatureof the other band.
 4. The system of claim 2 wherein the other portion isproximate the sample.
 5. The system of claim 4 wherein the other bandsupports the sample stage.
 6. The system of claim 1 wherein theanalytical attachment is an objective.
 7. The system of claim 6 whereinthe attachment and/or sample stage are maintained under vacuum.
 8. Thesystem of claim 7 configured for cryogenic analysis.
 9. The system ofclaim 1 wherein the structure is sufficiently pliable to provide supportbut allow for expansion and/or contraction of related portions and/orbands.
 10. The system of claim 1 wherein the analytical attachment isfirmly affixed to the one band, and the analytical attachment is axiallyaligned with the sample stage.
 11. The system of claim 10 wherein theinstrument is configured to have a temperature gradient between the oneband and the sample stage while maintaining axial alignment of theanalytical attachment and the sample stage.
 12. The system of claim 1wherein the analytical attachment is a microscope objective and themicroscope objective and sample are both under vacuum.
 13. The system ofclaim 1 further comprising a constant distance between the analyticalattachment and the sample stage.